Latin American young patients with gastric adenocarcinoma: worst prognosis and outcomes.

Background: Incidence of young patients (aged 40 years or younger) diagnosed with gastric carcinoma has increased worldwide. Young GC diagnosis, have clinicopathological features that differ from elderly, and is correlated with bad prognosis factors. The purpose of this work is to describe the prevalence, clinic-pathological features, and prognosis of overall survival (OS) of young Latin-American patients with GC. Methods: Retrospective, observational study. Included patients treated at the National Cancer Institute [2004-2020]. Statistical analysis: χ2 and t-test, Kaplan-Meier, Log-Rank and Cox-Regression. Statistical significance differences were assessed when P was bilaterally <0.05. Results: A total of 2,543 patients fulfilled the inclusion criteria. Young-patients were predominantly female (54%), with diffuse-type adenocarcinoma (68%), signet-ring-cell (72%), poor-differentiation (90%), and metastatic (79%). In OS analysis, patients with metastatic disease, showed differences regarding age, young patients reported a median-OS of 8 versus 13 months for elderly patients (P=0.001). Among young patients, differences were also observed regarding gender, young-female patients had a median-OS of 5 versus 11 months for young-man (P=0.001). Conclusions: This is one of the pioneer studies correlating age with gender and the prognostic features of bad prognosis in Latin-American population. Besides, supports the idea that a global effort is required to improve awareness, prevention, and early diagnosis of GC.

Impact of ileostomy in the adjuvant treatment and outcome of colon cancer.

BACKGROUND: After tumor resection, a preventive diverting loop ileostomy creation is a routine surgical procedure to prevent anastomotic leakage and infections and to preclude secondary surgeries. Despite its benefits, several studies have proposed potential complications that extend the disease course by impairing the feasibility of adjuvant chemotherapy and adherence. PURPOSE: The aim of this study was to evaluate the impact of ileostomy complications on the adherence to adjuvant treatment and overall survival (OS) of colon cancer (CC) patients. METHODS: Retrospective, observational study. Patients diagnosed with colon adenocarcinoma were treated between January 2010 and December 2020 at the National Cancer Institute in Mexico. STATISTICAL ANALYSIS: χ2 and t-test, Kaplan-Meier, log-rank, and Cox regression. Statistical significance differences were assessed when p was bilaterally < 0.05. RESULTS: The most frequent complications of loop-derived ileostomy were hydro-electrolytic dehydration (50%), acute kidney injury (AKI) (26%), grade 1-2 diarrhea (28%), and grade 3-4 diarrhea (21%) (p = 0.001). Patients with complete chemotherapy did not reach the median OS. In contrast, the median OS for patients with non-complete chemotherapy was 56 months (p = 0.023). Additionally, 5-year OS reached to 100% in the early restitution group, 85% in the late restitution group, and 60% in the non-restitution group (p = 0.016). Finally, AKI (p = 0.029; 95% confidence interval (CI) 3.348 [1.133-9.895]), complete chemotherapy (p = 0.028; 95% CI 0.376 [0.105-0.940]), and reversed ileostomy (p = 0.001; 95% CI 0.125 [0.038-0.407]) remained as predictors of overall survival for patients with CC treated with a loop ileostomy. CONCLUSIONS: Our results emphasize the early stoma reversal restitution as a safe and feasible alternative to prevent severe complications related to ileostomies which improve chemotherapy adherence and overall survival of colon cancer patients. This is one of the pioneer studies analyzing the impact of ileostomy on treatment adherence and outcome of Latin American patients with colon cancer. TRIAL REGISTRATION: Retrospective study No. 2021/045, in April 2021.

Progress in Metabolic Studies of Gastric Cancer and Therapeutic Implications.

BACKGROUND: Worldwide, gastric cancer is ranked the fifth malignancy in incidence and the third malignancy in mortality. Gastric cancer causes an altered metabolism that can be therapeutically exploited. OBJECTIVE: The objective of this study is to provide an overview of the significant metabolic alterations caused by gastric cancer and propose a blockade. METHODS: A comprehensive and up-to-date review of descriptive and experimental publications on the metabolic alterations caused by gastric cancer and their blockade. This is not a systematic review. RESULTS: Gastric cancer causes high rates of glycolysis and glutaminolysis. There are increased rates of de novo fatty acid synthesis and cholesterol synthesis. Moreover, gastric cancer causes high rates of lipid turnover via fatty acid ß-oxidation. Preclinical data indicate that the individual blockade of these pathways via enzyme targeting leads to antitumor effects in vitro and in vivo. Nevertheless, there is no data on the simultaneous blockade of these five pathways, which is critical as tumors show metabolic flexibility in response to the availability of nutrients. This means tumors may activate alternate routes when one or more are inhibited. We hypothesize there is a need to simultaneously block them to avoid or decrease the metabolic flexibility that may lead to treatment resistance. CONCLUSION: There is a need to explore the preclinical efficacy and feasibility of combined metabolic therapy targeting the pathways of glucose, glutamine, fatty acid synthesis, cholesterol synthesis, and fatty acid oxidation. This may have therapeutical implications because we have clinically available drugs that target these pathways in gastric cancer.

Simultaneous expression of steroid sulfatase and androgen receptor reduced overall survival of patients with epithelial ovarian tumors.

BACKGROUND: Ovarian cancer is usually diagnosed at an advanced stage due to its early asymptomatic course and late-stage non-specific symptoms. This highlights the importance of researching the molecular mechanisms involved in ovarian carcinogenesis as well as the discovery of novel prognostic markers that could help improve the survival outcome of patients. The aim of this study was to evaluate the expression of the steroid sulfatase (STS) in 154 samples of primary ovarian tumors. This protein is crucial in the intracellular conversion of sulfated steroid hormones to active steroid hormones. The presence of STS, 3ß-HSD, and 17ß-HSD1 result in the production of testosterone which act through the androgen receptor (AR) in the tumor cell. The presence of STS and AR in epithelial ovarian tumors and their association to the overall survival of patients was evaluated using Kaplan-Meier and Cox regression analyses. RESULTS: Immunoreactivity for STS was detected in 65% of the tumors and no association was observed with histological subtypes and clinical stages of the tumor. The STS expression in the tumors exhibiting immunoreactive AR resulted in a reduced survival (log-rank test, p = 0.032) and a risk factor in univariate and multivariate analysis, HR = 3.46, CI95% 1.00-11.92, p = 0.049 and HR = 5.92, CI95% 1.34-26.09, p = 0.019, respectively. CONCLUSIONS: These findings suggest that the intracellular synthesis of testosterone acting through its receptor can promote tumor growth and progression. Moreover, the simultaneous expression of STS and AR constitutes an independent predictor of poor prognosis in epithelial ovarian tumors.

Clinically Relevant Response to Treatment with Olaparib in a Patient with Refractory Multidrug-Resistant Ovarian Cancer and Central Nervous System Involvement: A Case Report.

BACKGROUND Despite advances in diagnosis and treatment, epithelial ovarian cancer (EOC) continues to be highly lethal. Undoubtedly, the introduction of poly(adenosine diphosphate-ribose) polymerase inhibitors such as olaparib will alter this clinical picture. Phase III studies have already documented clinically relevant outcomes, particularly among patients with BRCA mutations and homologous recombination deficiency. CASE REPORT Here we present a case report that documents the evolution of refractory multidrug-resistant, BRCA1-mutated EOC in a patient who had advanced clinical deterioration, carcinomatosis, and central nervous system (CNS) involvement that responded favorably to olaparib, resulting in a tripling of her progression-free survival. CONCLUSIONS Olaparib proved to be a safe and effective option for the treatment of a patient with multidrug-resistant, BRCA1-mutated EOC with CNS metastases. This suggests that early initiation of the drug in similar cases can be very useful.

Expression of metalloproteinases MMP-2 and MMP-9 is associated to the presence of androgen receptor in epithelial ovarian tumors.

BACKGROUND: The current study evaluated the metalloproteinases MMP-2 and MMP-9 expression in epithelial cells and the surrounding stroma in ovarian tumors and the association of MMPs with the histological subtypes, the clinical stage and the presence of steroid hormone receptors. Tumor samples were obtained from 88 patients undergoing surgical cytoreduction of primary ovarian tumors in Instituto Nacional de Cancerología, from México City. The formalin fixed and paraffin embedded samples were processed in order to demonstrate the presence of androgen receptor,estrogen receptor alpha, progesterone receptor, MMP-2,MMP-9 and collagen IV by immunohistochemistry and/or immunofluorescence. RESULTS: MMP-2 and MMP-9 were differentially expressed in the epithelium and the stroma of ovarian tumors associated to histological subtype, clinical stage and sexual steroid hormone receptor expression. Based on Cox proportional hazard regression model we demonstrated that MMP-2 located in the epithelium and the stroma are independent prognostic biomarkers for overall survival in epithelial ovarian tumors. Kaplan Meir analysis of the combination of AR (+) with MMP-2 (+) in epithelium and AR (+) with MMP-2 (-) in stroma displayed a significant reduction of survival. CONCLUSIONS: The presence of MMP-2 in the stroma of the tumor was a protective factor while the presence of MMP-2 in the epithelium indicated an adverse prognosis. The presence of AR associated with MMP-2 in the tumor cells was a risk factor for overall survival in epithelial ovarian cancer.

High levels of pretreatment CA125 are associated to improved survival in high grade serous ovarian carcinoma.

BACKGROUND: Serum levels of CA125 measured before any treatment have been evaluated in epithelial ovarian cancer (EOC) as a predictor of patient survival; however, results in survival index are controversial, as CA125 levels are influenced by several variables. Taking this into consideration, the present study evaluated the association of pretreatment levels of CA125 serum with the clinical stage, histology and differentiation grade of the tumor and the survival rate in a group of patients from an oncology referral center in Mexico, all of them diagnosed with ovarian carcinoma. This retrospective study consisted of 1009 patients with EOC, diagnosed between 2006 and 2013 at the National Cancerology Institute (Instituto Nacional de Cancerología-INCan), considering only those with CA125 measurements before any chemotherapy or surgical cytoreduction. Patients with three years of medical follow-up having pretreatment CA125 value and simultaneous diagnoses of histological subtype, clinical stage and differentiation grade of the tumor (n = 656) were studied in order to determine their survival rate. RESULTS: The abnormal level (>35 U/mL) of CA125 was observed in 99 % of serous carcinoma cases rated I to IV in the FIGO stages. Abnormal CA125 proportions were 89 % in endometrioid subtype and 69 % in mucinous tumors, with the highest absolute value of CA125 observed in serous carcinoma surpassing any other histological subtype. Clinical stages III and IV displayed increased CA125 values compared to stages I and II. Undifferentiated carcinomas show the highest level of this indicator compared with those of low and moderate differentiated grade. Survival evaluation by Kaplan-Meier analysis including only high grade serous carcinoma at FIGO stage III (n = 57) demonstrated 57.1 % chances of survival in patients with CA125 pretreatment levels higher than 500 U/mL. Survival was 26.7 % in patients with CA125 lower than 500 U/mL and the hazard ratio for CA125 ≤ 500 U/mL was 2.28, 95 % CI 1.08-4.84, P = 0.032. CONCLUSIONS: Clinical stage associated with pretreatment absolute values of CA125 should be considered as prognostic factor in EOC patients. Values of CA125 higher than 500 U/mL in high grade serous carcinoma with FIGO stage III resulted in an enhanced survival rate of the patients.

Gastric cancer in young people under 30 years of age: worse prognosis, or delay in diagnosis?

BACKGROUND: Gastric cancer is an aggressive disease with nonspecific early symptoms. Its incidence and prognosis in young patients has shown considerable variability. PURPOSE OF THE STUDY: Our objective was to retrospectively study patients from our institution aged <30 years with gastric carcinoma. The study was undertaken to describe the experience of gastric cancer in this population, and to demonstrate its specific clinical and pathological characteristics. MATERIALS AND METHODS: We reviewed the cases of histologically confirmed gastric cancer between 1985 and 2006 at the Instituto Nacional de Cancerología of Mexico (INCan); emphasis in our review was placed on clinical presentation, diagnostic and therapeutic intervention, pathology, and the results. RESULTS: Thirty cases of gastric carcinoma were reviewed. The patients' median age was 27 years (range, 18-30 years) and the male:female ratio was 1:1. CONCLUSION: Gastric cancer exhibits different behavior in patients aged, 30 years, but delay in diagnosis and the tumor's behavior appear to be the most important factors in prognosis of the disease.

[Open splenectomy: ten-year experience in an oncological referral center]. / Esplenectomía a cielo abierto. Experiencia de 10 años en un centro oncológico.

BACKGROUND: Open splenectomy is a useful procedure for some diseases with splenomegaly >1500 g. We undertook this study to evaluate open splenectomy morbidity and mortality at the Instituto Nacional de Cancerologia in Mexico City. METHODS: We reviewed the clinical files of patients with benign and malignant hematological diseases, as well as other diseases, who underwent splenectomy from 1994 to 2005. RESULTS: Twenty five patients with a mean age of 38.5 years were submitted for open splenectomy. Splenomegaly was found in 12 patients (48%). The most frequent abdominal wall incision was transverse left subcostal (64%). Average surgical time was 125 min, bleeding 485 ml, spleen weight 1553.6 g and mean size 15 x 11 x 12 cm. Mean hospital stay was 7.5 days. Eighteen patients (72%) did not have immediate complications. One patient (4%) developed surgical wound infection, two patients (8%) had significant pain, three patients (12%) had bleeding and one patient (4%) developed intraabdominal fluid collection. Twenty one patients (84%) did not have further complications. One patient (4%) developed multiple organ failure, another patient (4%) developed thrombocytopenia and another (4%) developed severe pain. During an average 81-month follow-up we found 14 patients (56%) asymptomatic, two patients (8%) with documented tumoral activity (angiosarcoma and non-Hodgkin's lymphoma) and one patient (4%) developed a second neoplasm. Six patients (24%) died due to underlying disease (chronic myeloid leukemia and lymphoma), one patient (4%) with active disease (Hodgkin's disease) and one patient (4%) died due to other causes. CONCLUSIONS: With a spleen >1500 g, open surgery offers better visibility and, in fact, less morbidity and mortality.